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Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin\u2010positive neurons.<\/jats:p><\/jats:sec>Objective<\/jats:title>The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon\u2010gamma (IFN<\/jats:styled-content>\u03b3) production from immune cells in response to molecularly defined targets.<\/jats:p><\/jats:sec>Methods<\/jats:title>Cellular reactivity defined by IFN<\/jats:styled-content>\u03b3 production was examined in blood from 38 (HLA<\/jats:styled-content>\u2010DQB<\/jats:styled-content>1*06:02<\/jats:italic>+<\/jats:sup>) Pandemrix\u2010vaccinated narcolepsy cases and 76 (23 HLA<\/jats:styled-content>\u2010DQB<\/jats:styled-content>1*06:02<\/jats:italic>+<\/jats:sup> and 53 HLA<\/jats:styled-content>\u2010DQB<\/jats:styled-content>1*06:02<\/jats:italic>\u2212<\/jats:sup>) control subjects, matched for age, sex and exposure, using a variety of different antigens: \u03b2\u2010haemolytic group A streptococcal (GAS<\/jats:styled-content>) antigens (M5, M6 and streptodornase B), influenza (the pandemic A\/H1N1\/California\/7\/09 NYMC<\/jats:styled-content> X\u2010179A and A\/H1N1\/California\/7\/09 NYMC<\/jats:styled-content> X\u2010181 vaccine antigens, previous Flu\u2010A and \u2010B vaccine targets, A\/H1N1\/Brisbane\/59\/2007, A\/H1N1\/Solomon Islands\/3\/2006, A\/H3N2\/Uruguay\/716\/2007, A\/H3N2\/Wisconsin\/67\/2005, A\/H5N1\/Vietnam\/1203\/2004 and B\/Malaysia\/2506\/2004), noninfluenza viral targets (CMV<\/jats:styled-content>pp65, EBNA<\/jats:styled-content>\u20101 and EBNA<\/jats:styled-content>\u20103) and auto\u2010antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue).<\/jats:p><\/jats:sec>Results<\/jats:title>IFN<\/jats:styled-content>\u2010\u03b3 production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0065) and streptodornase B protein (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0050). T\u2010cell recognition of M6 and streptodornase B was confirmed at the single\u2010cell level by intracellular cytokine (IL<\/jats:styled-content>\u20102, IFN<\/jats:styled-content>\u03b3, tumour necrosis factor\u2010alpha and IL<\/jats:styled-content>\u201017) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>\u03b2\u2010haemolytic GAS<\/jats:styled-content> may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes<\/jats:italic> M\u2010type\u2010specific IFN<\/jats:styled-content>\u2010\u03b3 cellular immune response.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12355","type":"journal-article","created":{"date-parts":[[2015,2,14]],"date-time":"2015-02-14T07:23:09Z","timestamp":1423898589000},"page":"264-276","source":"Crossref","is-referenced-by-count":33,"title":["Increased \u03b2\u2010haemolytic group A streptococcal M6 serotype and streptodornase B\u2010specific cellular immune responses in Swedish narcolepsy cases"],"prefix":"10.1111","volume":"278","author":[{"given":"A.","family":"Ambati","sequence":"first","affiliation":[{"name":"Department of Medicine Karolinska Institutet Stockholm Sweden"},{"name":"Centre for Allogeneic Stem Cell Transplantation Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Poiret","sequence":"additional","affiliation":[{"name":"Division of Therapeutic Immunology Department of Laboratory Medicine Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.\u2010M.","family":"Svahn","sequence":"additional","affiliation":[{"name":"Centre for Allogeneic Stem Cell Transplantation Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Valentini","sequence":"additional","affiliation":[{"name":"Centre for Allogeneic Stem Cell Transplantation Karolinska University Hospital 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